α‐Aminophosphonates as novel organocatalysts for asymmetric Michael addition of carbonyl compounds to nitroolefins

Abstract

A cyclic alpha-aminophosphonate was found to be a novel organocatalyst for Michael type addition reactions of carbonyl compounds to nitroolefins to afford the corresponding adducts in high enantio- and diastereoselectivities.

Synthetic methods of cyclic α-aminophosphonic acids and their esters

“…[58][59][60][61][62] Hydrogenolysis of 82, followed by acidic hydrolysis of the phosphonate moiety with 6 M HCl and subsequent treatment with propylene oxide led to (S)-phosphopyrrolidine 25 (Scheme 30). …”

Facile synthesis of cyclic α-perfluoroalkyl-α-aminophosphonates

“…Being analogous to amino acids they found applications as antibiotics [2], proteolytic enzyme inhibitors [3], anti-cancer agents [4], and herbicides [5]. a-Aminophosphonates are also of undoubted interest as ligands in homogeneous [6,7] or organic [8,9] catalysis.…”

Catalytic Asymmetric 1,2‐Addition of α‐Isothiocyanato Phosphonates: Synthesis of Chiral β‐Hydroxy‐ or β‐Amino‐Substituted α‐Amino Phosphonic Acid Derivatives

“…Naturally occurring [1] and synthetic compounds incorporating such units are widely used in the fields of medicinal chemistry, [2] agriculture, [2c] metallurgy [3] and asymmetric catalysis. [4] Because of their practical importance, such organophophoric molecules have drawn tremendous interest from synthetic and medicinal chemists. [5] Since it is well known that the chirality of the a-carbon center is critical for the properties of the a-amino phosphonic acid derivatives, enantiomerically controlled synthesis is essential, and a number of elegant catalytic asymmetric syntheses have reported.…”

“…To enhance the reactivity of the isothiocyanates, the diphenyl phosphonate 1 b was then tested, and to our delight, it gave the adduct in an increased yield at 30 8C (83 %; Table 1, entry 2). Next, several tertiary amine-thioureas with different types of structural scaffold, namely cinchonine, cyclohexanediamine, and binaphthylamine, were screened ( Table 1, entries [3][4][5]. However, the enatioselectivity of the reaction was still moderate.…”

“…To our delight, the same conditions were suitable for the new process and no further optimization was needed ( Table 3, entry 1). Imines with both electron-donating and electron-withdrawing substituents at different positions on the phenyl ring gave the corresponding products with good results in terms of yield and stereocontrol ( Table 3, entries [1][2][3][4][5][6][7][8]. A substrate containing a heteroaromatic ring was also tolerated ( Table 3, entry 9).…”